Tag Archives: CB1

Pharmacological synergism between cannabinoids and paclitaxel in gastric cancer cell lines.

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“Orally applicable Delta9-tetrahydrocannabinol and its synthetic derivatives have been used as antiemetic drugs during chemotherapy in cancer patients.

 However, it is not well known how cannabinoids influence the effects of chemotherapeutic agents on malignant tumors. In this study, we investigated how the endogenous cannabinoid anandamide (AEA) changes the effect of paclitaxel on gastric cancer cell lines.

 In the human gastric cancer cell line, HGC-27, which express cannabinoid receptor 1 (CB1), AEA stimulated proliferation at concentrations under 1 microM, while it strongly suppressed proliferation through the induction of apoptosis at 10 microM. This bimodal effect was reproduced by a selective CB1 agonist, arachidonyl-2-chloroethylamide, although the effects were less marked. When AEA was used with paclitaxel, AEA at 10 microM synergistically enhanced the cytotoxic effect of paclitaxel, whereas it showed no significant effect at lower concentrations. Flow cytometric analysis revealed that addition of 10 microM AEA synergistically enhanced paclitaxel-induced apoptosis, possibly through the activation of caspase-3, -8, and -9.

Our results suggest that cannabinoids could be a good palliative agent for cancer patients receiving paclitaxel.”

http://www.ncbi.nlm.nih.gov/pubmed/19394652

The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity

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“Δ9-Tetra-hydrocannabivarin (THCV) is a naturally occurring analogue of the psychoactive principle of cannabis, Δ9-tetra-hydrocannabinol (THC).

THCV is a new potential treatment against obesity-associated glucose intolerance with pharmacology different from that of CB1 inverse agonists/antagonists.

In conclusion, THCV produces therapeutic metabolic effects in two different mouse models of obesity. In particular, its strongest effects are exerted on plasma glucose and insulin levels, especially following an OGTT in DIO mice and on liver triglycerides in ob/obmice.

Based on these data, it can be suggested that THCV may be useful for the treatment of the metabolic syndrome and/or type 2 diabetes, either alone or in combination with existing treatments. Given the reported benefits of another non-THC cannabinoid, CBD in type 1 diabetes, a CBD/THCV combination may be beneficial for different types of diabetes mellitus.”

Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671751/

Marijuana and its receptor protein in brain control epilepsy

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“VCU study is first to test anticonvulsant potential of marijuana and brain recurrent seizures. 

Ingredients in marijuana and the cannabinoid receptor protein produced naturally in the body to regulate the central nervous system and other bodily functions play a critical role in controlling spontaneous seizures in epilepsy, according to a new study by researchers at Virginia Commonwealth University.

The study, the first to look at marijuana and the brain’s cannabinoid system in live animals with spontaneous, recurrent seizures, suggests new avenues that researchers can explore in their search for more-effective drugs to treat epileptic patients who don’t respond to today’s anticonvulsant medications or surgery.

The results appear in the Oct. 1 issue of the Journal of Pharmacology and Experimental Therapeutics.

“Although marijuana is illegal in the United States, individuals both here and abroad report that marijuana has been therapeutic for them in the treatment of a variety of ailments, including epilepsy,” says Dr. Robert J. DeLorenzo, professor of neurology in the VCU School of Medicine.

 “If we can understand how marijuana works to end seizures, we may be able to develop novel drugs that might do a better job of treating epileptic seizures.” 

Epilepsy is one of the most common neurological conditions, characterized by spontaneously recurrent seizures. Approximately 1 percent of Americans have epilepsy, and 30 percent of those patients are resistant to conventional anticonvulsant drug treatments.

Cannabinoids have been used as a natural remedy for seizures for thousands of years, and studies since at least 1974 have found that the primary psychoactive compound in marijuana displays anticonvulsant properties.” 

More:http://www.news.vcu.edu/news/Marijuana_and_its_receptor_protein_in_brain_control_epilepsy

Association between Cannabinoid CB1 Receptor Expression and Akt Signalling in Prostate Cancer

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“In prostate cancer, tumour expression of cannabinoid CB1 receptors is associated with a poor prognosis. One explanation for this association comes from experiments with transfected astrocytoma cells, where a high CB receptor expression recruits the Akt signalling survival pathway. In the present study, we have investigated the association between CB1 receptor expression and the Akt pathway in a well-characterised prostate cancer tissue microarray.

Conclusions/Significance

The present study provides data that is consistent with the hypothesis that at a high CB1 receptor expression, the Akt signalling pathway becomes operative.”

Full Text: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0065798

Transient changes in the endocannabinoid system after acute and chronic ethanol exposure and abstinence in the rat: a combined PET and microdialysis study.

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“Recent biochemical and post-mortem evidence suggests involvement of the endocannabinoid system in alcohol drinking behaviour and dependence…

CONCLUSION:

This study provides in vivo evidence that acute ethanol consumption is associated with enhanced endocannabinoid signalling in the NAcc, indicated by an increased CB1R binding and AEA content. In addition, chronic ethanol exposure leads to regional dysfunctions in CB1R levels, involving the hippocampus and caudate-putamen that are reversible within 2 weeks in this animal model.”

http://www.ncbi.nlm.nih.gov/pubmed/23740372

Cannabinoid (CB)1 receptors are critical for the innate immune response to TLR4 stimulation.

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“Sickness behaviours are host defence adaptations that arise from integrated autonomic outputs in response to activation of the innate immune system. These behaviours include fever, anorexia, and hyperalgesia intended to promote survival of the host when encountering pathogens. Cannabinoid (CB) receptor activation can induce hypothermia and attenuate lipopolysaccharide (LPS)-evoked fever. The aim of the present study was to examine the role of CB1 receptors in the LPS-evoked febrile response. CB1 receptor-deficient (CB1-/-) mice did not display LPS-evoked fever; likewise pharmacological blockade of CB1 receptors in wild-type mice blocked LPS-evoked fever. This unresponsiveness is not limited to thermogenesis, as the animals were not hyperalgesic after LPS administration. A toll-like receptor (TLR)3 agonist and viral mimetic polyinosinic:polycytidylic acid evoked a robust fever in CB1-/- mice suggesting TLR3-mediated responses are functional. LPS-evoked c-Fos activation in areas of the brain associated with the febrile response was evident in wild-type mice but not in CB1-/- mice. Liver and spleen TLR4 mRNA were significantly lower in CB1-/- mice compared to wild-type, and peritoneal macrophages from CB1-/- mice did not release pro-inflammatory cytokines in response to LPS. These data indicate that CB1 receptors play a critical role in LPS-induced febrile responses through inhibiting TLR4-mediated cytokine production.”

http://www.ncbi.nlm.nih.gov/pubmed/23739343

Synthetic and Patented Cannabinoids

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“Historically, laboratory synthesis of cannabinoids were often based on the structure of herbal cannabinoids, and a large number of analogs have been produced and tested, especially in a group led by Roger Adams as early as 1941 and later in a group led by Raphael Mechoulam.

Newer compounds are no longer related to natural cannabinoids or are based on the structure of the endogenous cannabinoids.

Synthetic cannabinoids are particularly useful in experiments to determine the relationship between the structure and activity of cannabinoid compounds, by making systematic, incremental modifications of cannabinoid molecules.

Medications containing natural or synthetic cannabinoids or cannabinoid analogs:

  • Dronabinol (Marinol), is Δ9-tetrahydrocannabinol (THC), used as an appetite stimulant, anti-emetic, and analgesic
  • Nabilone (Cesamet), a synthetic cannabinoid and an analog of Marinol. It is Schedule II unlike Marinol, which is Schedule III
  • Sativex, a cannabinoid extract oral spray containing THC, CBD, and other cannabinoids used for neuropathic pain and spasticity in Canada and Spain. Sativex develops whole-plant cannabinoid medicines
  • Rimonabant (SR141716), a selective cannabinoid (CB1) receptor antagonist used as an anti-obesity drug under the proprietary name Acomplia. It is also used for smoking cessation

Other notable synthetic cannabinoids include:

  • CP-55940, produced in 1974, this synthetic cannabinoid receptor agonist is many times more potent than THC
  • Dimethylheptylpyran
  • HU-210, about 100 times as potent as THC
  • HU-331 a potential anti-cancer drug derived from cannabidiol that specifically inhibits topoisomerase II.
  • SR144528, a CB2 receptor antagonists
  • WIN 55, a potent cannabinoid receptor agonist
  • JWH-133, a potent selective CB2 receptor agonist
  • Levonantradol (Nantrodolum), an anti-emetic and analgesic but not currently in use in medicine”

http://www.news-medical.net/health/Synthetic-and-Patented-Cannabinoids.aspx

Cannabinoid Receptors

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“Before the 1980s, it was often speculated that cannabinoids produced their physiological and behavioral effects via nonspecific interaction with cell membranes, instead of interacting with specific membrane-bound receptors.

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate.

These receptors are common in animals, and have been found in mammals, birds, fish, and reptiles.

At present, there are two known types of cannabinoid receptors, termed CB1 and CB2, with mounting evidence of more.

Cannabinoid receptor type 1

CB1 receptors are found primarily in the brain, to be specific in the basal ganglia and in the limbic system, including the hippocampus.

They are also found in the cerebellum and in both male and female reproductive systems. CB1 receptors are absent in the medulla oblongata, the part of the brain stem responsible for respiratory and cardiovascular functions. Thus, there is not a risk of respiratory or cardiovascular failure as there is with many other drugs. CB1 receptors appear to be responsible for the euphoric and anticonvulsive effects of cannabis.

Cannabinoid receptor type 2

CB2 receptors are almost exclusively found in the immune system, with the greatest density in the spleen.

While found only in the peripheral nervous system, a report does indicate that CB2 is expressed by a subpopulation of microglia in the human cerebellum.

CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis.”

http://www.news-medical.net/health/Cannabinoid-Receptors.aspx

Dysregulation of Cannabinoid CB1 Receptor and Associated Signaling Networks in Brains of Cocaine Addicts and Cocaine-Treated Rodents.

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The endocannabinoid system is implicated in the neurobiology of cocaine addiction. This study evaluated the status of cannabinoid CB1 and CB2 receptors, the endocytic cycle of CB1 receptors, receptor regulatory kinases (GRK), and associated signaling (mTOR and p70S6K) in brain cortex of drug abusers and cocaine- and cannabinoid-treated rodents…

 In long-term cocaine addicts, mTOR and p70S6K activations were not altered when compared with controls, indicating that CB1 receptor signaling was dampened. The dysregulation of CB1 receptor, GRK2/3/5, and mTOR/p70S6K signaling by cocaine may contribute to alterations of neuroplasticity and/or neurotoxicity in brains of cocaine addicts.”

More: http://www.ncbi.nlm.nih.gov/pubmed/23727505

Marijuana May Cure PTSD – NBC

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“Veterans suffering from post traumatic stress disorder may find help through marijuana.”

Cannabis Cup Cake Anyone?
  

“Could cannabis cure PTSD?

Post-traumatic stress disorder, which can also affect civilians who undergo a traumatic episode, may be cured by using marijuana, according to an East Bay Express report.

A researcher at Yale University is conducting a long-term study with 120 people — veterans with “intractable cases of PTSD” — who he thinks can be cured of their dehabilitating condition with marijuana.

Most people suffering from PTSD go through a regimen of drugs or more-invasive “exposure therapy,” in which they dig as deeply as possible into their trauma for 12 weeks. Most drop out in Week 3, according to the report.

The theory of R. Andrew Sewell is that tetrahydrocannabinol, or THC, one of the active ingredients in cannabis, can help the brain learn new information. This in turn helps people suffering from PTSD forget the old — as in bad — information.

This is called “extinction learning,” Sewell says. And such learning is made easier when a “switch” in the brain called CB1 is activated. It turns out cannabis is very good at activating the CB1 receptor.

“We’re talking about a cure,” said Sewell, who noted that after treatment, no drugs — not cannabis and not antidepressants — would be required.”

http://www.nbcbayarea.com/news/local/Marijuana-May-Cure-PTSD-208900021.html